A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Ocrelizumab in Children and Adolescents with Relapsing-Remitting Multiple Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

18 Oct 2019 → ongoing

Decision date (initial)

2023-12-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-507313-94-00

EudraCT number

2016-002667-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Pharmacokinetic

To characterize the ocrelizumab pharmacokinetic (PK) profile in children and adolescents. To evaluate relationship between drug exposure and pharmacodynamic (PD) (cluster of differentiation 19 [CD19] + B-cell count) in children and adolescents.

Secondary objectives 2

1. 1.To evaluate safety of ocrelizumab in children and adolescents
2. 2.To assess anti-drug antibody (ADA) development to ocrelizumab

Conditions and MedDRA coding

Relapsing-Remitting Multiple Sclerosis (RRMS)

Study design 4 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-000310-PIP03-10

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 1.Body weight >= 25 kg Note: enrollment of patients with a body weight >= 40 kg is closed
2. 2.Children and adolescents must have received all childhood vaccinations as per local/national recommendations for childhood vaccination against infectious diseases
3. 3.For female patients of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception including at least one method with a failure rate of < 1% per year, during the treatment period and for at least 24 weeks after the final dose of ocrelizumab. Adherence to local requirements, if more stringent, is required
4. 4.Diagnosis of RRMS in accordance with the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for pediatric multiple sclerosis (MS), Version 2012, and McDonald criteria 2017
5. 5.Expanded disability status scale (EDSS) at screening: 0-5.5, inclusive
6. 6.Patients who have had at least 6 continuous months of disease-modifying therapy (DMT) (e.g., any interferon [IFN] or glatiramer acetate [GA]) within the past 1 year must have evidence of disease activity occurring after the full 6-month course of treatment, that is, at least one relapse or >= 1 gadolinium (Gd)-enhancing lesion(s) on a T1-weighted brain magnetic resonance imaging (MRI)

Exclusion criteria 6

1. 1.Known presence or suspicion (based on clinical or laboratory parameters) of other neurologic disorders that may mimic MS, including, but not limited to, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica or neuromyelitis optica spectrum disorders; and any neurologic (other than MS), somatic, or metabolic condition that could interfere with brain function or normal cognitive or neurological development. Patients that are aquaporin 4 positive and myelin oligodendrocyte glycoprotein (MOG) antibody positive are not eligible to participate in the study
2. 2.Atypical MRI findings: ADEM-like presentation of lesions; lesions in atypical location for MS; bilateral soptic neuritis; extensive spinal cord lesions (>= 3 spinal segments)
3. 3.Known active bacterial, viral, fungal, mycobacterial infection, or other infection, excluding fungal infection of nail beds
4. 4.Receipt of a live or live-attenuated vaccine within 6 weeks prior to treatment allocation. The patient's vaccination record and a need for immunization should be carefully reviewed (scheduled vaccinations should be completed at least 6 weeks prior to receiving ocrelizumab, according to local guidelines)
5. 5.History of a severe allergic or anaphylactic reaction to humanized or murine monoclonal antibodies (mAbs) or known hypersensitivity to any component of ocrelizumab solution
6. 6.Positive screening tests for hepatitis B (hepatitis B surface antigen [HBsAg] positive, or positive hepatitis B core antibody [total HBcAb] confirmed by a positive viral deoxyribonucleic acid [DNA] polymerase chain reaction [PCR]) or hepatitis C antibody (HepCAb)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 1.Serum concentration of ocrelizumab at specified timepoints
2. 2.Levels of CD19+ B-cell count in blood

Secondary endpoints 9

1. 1.Occurrence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0)
2. 2.Change from baseline in vital signs
3. 3.Change from baseline in clinical laboratory test results
4. 4.Level of circulating B cells, T cells, natural killer cells, and other leukocytes
5. 5.Developmental milestones (e.g., growth, bone age, age at menarche, Tanner staging)
6. 6.Non-MS central nervous system (CNS) pathology as measured by brain MRI scans
7. 7.Levels of blood immunoglobulins
8. 8.Antibody titers against standard vaccines
9. 9.Presence of ADAs during the study relative to the presence of ADAs at baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 4

Locations

2 EU/EEA countries · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications